Peppermint; Human diseases; Peppermint oil; Quantum chemistry;
PO: Peppermint oil; WHO: World Health Organization; HOMO:
The highest occupied molecule orbital LUMO: The lowest
un-occupied molecular orbital; MEP: Molecular electrostatic
potentials; NAT: Arylamine N- acetyltransferase; SD: Standard
deviation; IBS: Irritable bowel syndrome; HSV=Herpes simplex virus (DNA virus); VACV=Vaccinia virus
Medicinal plants have received more attention because of their
health benefits, such as anti-infectious properties, since ancient
times [1-6]. The term of medical plants is referred to the natural
remedies that have used for treatment of human diseases [4,7-10]. These medicinal plants can be considered as a valuable
source of ingredients which can be used in drug development
[5,11-13]. On the other hand, medical plants significantly
affected the human life across the entire world [5,7,14,15]. The
use of herbal medicine is leading modality, followed in Middle
East, Europe and certain other advance countries, in order to
treat of catastrophic human diseases . Based on the WHO
reports, the advanced countries have used medicinal plant for
both clinical therapy and food industries significantly [16,17].
Medicinal plants have significant potentials for human societies
and consumed by people across the entire world. Although most of their health benefits have not investigated yet, their medical
activities can be considered in the treatment of present or future
diseases . Currently, more than 80% of the world population
use the traditional medicine and medicinal plants (especially plant
extracts and essential oils) for their primary health needs .
Peppermint or mint (Mentha piperita L.), a perennial aromatic
herb belonging to the Lamiaceae (Labiatae) family, is a natural
hybrid between spearmint (Mentha spicata L.) and water mint
(Mentha aquatic L.) [19,20]. Although it is a native genus of the
Mediterranean regions, it cultivated all over the world for its use
in flavor, fragrance, medicinal, and pharmaceutical applications
. Members of the mint genus are characterized by their
volatile oils which are of great economic importance, being used
by the flavor, fragrance, and pharmaceutical industries .
This plant is widely used in folk remedies and traditional medicine
for treatment of digestive disorders and nervous system actions
because of its antitumor and antimicrobial properties, chemopreventive
potential, its renal actions, antiallergenic effects,
and also for lessening cramping, digestive complaints, anorexia, nausea and diarrhea [23,24]. Preparations of peppermint include
leafs, leaf extracts and water, however, the plant is cultivated
mainly for its essential oil, which is obtained by distillation from
freshly grounded leaves [25-28]. PO is composed of menthol and
menthone together with several other minor constituents,
including pulegone, menthofuran and limonene, and its chemical
composition may vary with plant maturity, geographical region
and processing conditions [28-30].
Menthol occurs naturally as a colorless crystal or powder . It
is greatly responsible for the spasmolytic nature of peppermint
. Menthol has reported to stimulate bile flow , reducing
the tone in the esophageal sphincter , facilitating belching
, as well as having antibacterial properties . In addition,
peppermint is also a rich source of polyphenolic compounds and
hence the strong antioxidant properties [8,22,26,28,37]. Among
all countries in the world, India is the largest producer, exporter
 and consumer of mint oil . Currently China is a major
importer of peppermint .
HOMO (highest occupied molecular orbital) and LUMO (lowest
unoccupied molecular orbital) orbitals are very important
parameters used in quantum chemistry [40-42]. Based on their
characteristics, it can be specified how a molecule would interact
with other molecules . The HOMO orbitals can be considered
as an electron donor group, while the LUMO orbitals as free sites
able to accept them [40,43-46]. Energy of the HOMO orbitals can
be directly linked to the ionization potential, whereas the LUMO
orbital energy can be associated with the electron affinity [40,44].
The difference between the orbital energies of HOMO and LUMO
is referred to as energy gap (ΔE) which is an important parameter
that can determine the reactivity or stability of molecules [40,44-46]. Since quantum chemistry and molecular docking studies
have not been reported, the present study aims at determining
the optimized molecular geometry, HOMO-LUMO energies of
peppermint main compounds, using Hartree-Fock, 3-21G basic
set and also indicates the binding mode of these compounds into
a selected receptor. Also, the most abundant medicinal benefits
of peppermint have reviewed.
Herein the therapeutic application of volatile oil of peppermint
is discussed and also chemical descriptors are calculated to
determine the electron parameters of peppermint active
constituents to search for biological activities of these compounds.
Molecular quantum studies
All computational calculations were performed at the Hartree-
Fock model on a Pentium IV/2.8 GHz personal computer using
Spartan 10 software Wavefunction, Inc. . The geometry of
the peppermint active constituents in the ground state is fully
The 3D structure of NAT enzyme (PDB ID: 2IJA) was obtained from
PDB database (http://www.rcsb.org/pdb/home/home.do) and
selected as receptor against peppermint chemical compounds.
The molecular docking (blind docking) was done by Molegro virtual Docker 4.2.0 version. Visualization of docking results was
performed by MOE software (https://www.chemcomp.com/MOE-Molecular_Operating_Environment.htm).
Nomenclature, botany and cultivation
Peppermint has more than 101 local names in different countries
(Table 1) [48-51]. The principle of naming of mint is considered
based on local culture and customs.
||Lab Mint, mint
||Urdu, mint, Pudina, Pudyana, Puthina
Table 1: The most abundant local names of mint around the world.
In botany, Mentha piperita L. is the common name for genus of
peppermint . The genus Mentha includes 25 to 30 species
 which is a perennial herb and native to Europe, naturalized
in the northern USA and Canada, and cultivated in many part of
the world [53,54].
The mint is a sterile hybrid of spearmint (Mentha spicata) and
water mint (Mentha aquatica) from the Lamiaceae family (Figure
Figure 1: A schematic illustration of peppermint hybrid.
The most relevant of mint species with commercial or medicinal
usage are listed in (Table 2).
||Medicine, Ornamental consumption, commercial
||Ornamental consumption, Medicine
Table 2 The list of the most abundant mint species and their functions.
Peppermint grows particularly well in lands with high waterholding
capacity soil [55-70]. All commercial mint varieties are
seed sterile and are propagated using the underground stolons
(runners or rootstock) produced by existing plants . The
stolons can’t be stored for more than a few days since they
deteriorate rapidly due to heat or dehydration . In general,
mints tolerate a wide range of conditions, and can also be grown
in full sun .
Many studies showed that peppermint essential oil is composed
of various secondary metabolites [27,28,31,33,34,38,53,54,73,74]. The mint main chemical compounds consist of limonene,
cineole, menthone, menthofuran, isomenthone, menthyl acetate, isopulegol, menthol, pulegone and carvone (Figure 2 and Table 3) [38,74].
Figure 2: Representation of the most abundant chemical compounds of PO.
||1 to 5
||3.5 to 14
||14 to 32
||1 to 9
||1.5 to 10
||Acetic acid [(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl] ester
||2.8 to 10
||30 to 55
Table 3 The most abundant active compounds of Mentha spp.
Other constituents include flavonoid glycoside (eg. Narirutin,
Luteolin-7-o-rutinoside, Isorhoifolin and Hesperidin etc) 
polyphenols (e.g Rosmaric acid, Eriocitrin, Cinamic acid, Caffeic
acid and Narigenin-7-oglucoside); luteolin-diglucoronide and
eriodictyol glucopyranosyl-rhamnopyranoside were also purified
from aerial parts of mint [75-79].
The amount of peppermint compounds is different in various
species . Various factors including physiological variations,
environmental conditions, geographic differences and genetic
factors cause differences in chemical composition of these plants .
The most abundant chemical compounds that isolated form
peppermint are largely classified into monoterpenes .
Currently, peppermint is the best model system for the study of
monoterpene metabolism . The pathway of monoterpene
biosynthesis in peppermint has been well characterized by in
vivo and systems biology studies (Figure 3) [83-85]. and all of the enzymes involved have been described [81,84]. According
to the traditional view [86,87] monoterpenes are amongst the
major constituents of essential oils and common secondary
metabolites of plant metabolism, and as such they generally
have been regarded as metabolic deadlock [83,84,87]. As shown
in figure 3, the peppermint monoterpene-derived compounds
separate from primary metabolism by conversion of isopentenyl
diphosphate and dimethylallyl diphosphate, via the action of the
prenyltransferase geranyl diphosphate synthase (EC 126.96.36.199), to
geranyl diphosphate, which undergoes subsequent cyclization
by limonene synthase (EC 188.8.131.52) to (4S)-(-)-limonene [84,88].
In peppermint a microsomal cytochrome (Cyt) P450 limonene-
3-hydroxylase (EC 184.108.40.206) adds an oxygen molecule in an
allylic location to produce (-)-trans-isopiperitenol and thereby
establishes the oxygenation pattern of all subsequent derivatives
Figure 3: A schematic illustration of metabolic pathway for biosynthesis of peppermint chemical compounds (The pathway is taken from KEGG database: http://www.genome.jp/kegg/).
A soluble NADP-dependent dehydrogenase (EC 220.127.116.11) oxidizes the alcohol to a ketone, (-)-isopiperitenone, thereby activating
the adjacent double bond for reduction by a soluble, NADPHdependent,
regiospecific reductase to afford (+)-cis-isopulegone.
An isomerase next moves the remaining double bond into
conjugation with the carbonyl group, yielding (+)-pulegone. A
NADPH-dependent reductase then converts (+)-pulegone to
(+)-isomenthone and (-)- menthone, which predominates .
Finally, two stereo-selective NADPH-dependent reductases
convert (-)-menthone and (+)-isomenthone to (-)-menthol
and (+)-neoisomenthol, respectively, and (-)-menthone and
(+)-isomenthone to (+)-neomenthol and (+)-isomenthol,
respectively [81,88,89]. In these pathways, (-)-limonene is the first
committed intermediate for biosynthesis of other compounds in
the peppermint species. However, production of monoterpenes
in peppermint id restricted to developing oil glands of young
leaves [88,90,91], and the correlation between in vitro activity
for the several enzymatic steps of menthol biosynthesis and the
rate of biosynthesis measured in vivo suggests that monoterpene
production is controlled by the coordinately regulated activity of
relevant biosynthetic enzymes [82,90,92]. As mentioned above,
(-)-Menthol greatly important among the menthol isomers (often
exceeding 50% of the essential oil) and is primarily responsible
for the characteristic flavor and cooling sensation of peppermint
HOMO and LUMO orbitals analysis
The HOMO and LUMO orbitals are very important in quantum chemistry calculations [95,96]. The HOMO energy determines the
electron donating ability while the LUMO designates the electron
accepting ability and the HOMO–LUMO energy gap (ΔEgap) (ELUMO-EHOMO) [97,98] is an important value for stability
index [96,99]. A large ΔEgap implies a good thermodynamic
stability of the compound, in the sense of its lower reactivity in
chemical reactions [100,101]. However, the magnitude of the
HOMO-LUMO gap has very important chemical implications,
even if qualitatively evaluated . To determine stability and
reactivity of peppermint main chemical compounds according
to Hartree-Fock model 3-21G basis set calculation for water
solution, the gap energies were measured (Table 4).
Table 4 HOMO and LUMO orbitals energy values for peppermint main
chemical compounds in water, calculated with Spartan 10 V1.1.0,
software, Hartree-Fock, 3-21G basic set.
Based on table 4 data, menthol, cineole and isopulegol have
higher stability than other compounds. The increase of stability
that showed by ΔEgap promotes the low reactivity of these
compounds in a chemical reaction. The relationship between ΔEgap energy, stability and reactivity is well known described in
many studies [103-105]. According to Hartree-Fock, 3-21G basic
set calculation, the highest and lowest gap energies is related
to menthol (16.9 eV), pulegone (12.6 eV) and carvone (12.6 eV)
respectively. Our result about stability of menthol is similar to
result that reported by Harlod and coworkers . Froehlich et
al. reported that in the aqueous ethanolic solutions, pulegone
was unstable and it can be degraded to other products .
This case confirmed our molecular orbitals analysis for pulegone.
Also, surfaces for the frontier orbitals were drawn to understand
the bonding scheme of present compounds. The features of
these molecular orbitals can be seen in (Figure 4).
Figure 4: The atomic orbital composition of the molecular orbital of peppermint-derived compounds. For interpretation of the references to color in this ﬁ gure, the reader is referred to the web version of this article.
The electrostatic potential of a molecule is an established tool
in medicinal chemistry, modeling, and computational chemistry
[108,109]. The MEP employed abundantly for predicting
potentials have been and interpreting the reactive behavior
of a wide range of chemical system in both electrophilic and
nucleophilic reactions, the study of biological recognition
processes and hydrogen bonding interactions [109-111]. To
predict reactive sites for electrophilic and nucleophilic attack for
the peppermint chemical compounds, MEP was calculated at
Hartree-Fock, 3-21G basic set optimized geometries. In the most
of the MEP, while the maximum negative site which preferred
region for electrophilic attack indications as red color, the
maximum positive region which preferred site for nucleophilic
attack symptoms as blue color [112,113]. In the present study, 3D
plot of molecular electrostatic potential of studied compounds
has been drawn in (Figure 5). In this plot the different values of
electrostatic potential at surface are represented by different
colors. Potential increase in order red<orange<yellow green<blue
Figure 5: Molecular electrostatic potential surface of peppermint active compounds. (For interpretation of the references to color in this ﬁgure, the reader is referred to the web version of this article).
As shown in (Figure 5), the regions having the negative potential
are over the electronegative atom oxygen, respectively. Thus,
it would be predicted that an electrophile would preferentially
attack peppermint compounds at the oxygen positions. In
addition, we found the positive regions over hydrogen atoms of
methyl group of peppermint compounds and indicating that these
sites can be the most probably involved in nucleophilic processes.
Red and blue colors in peppermint compounds map refer to the
regions of negative and positive potentials and correspond to
electron rich and electron-poor regions, respectively, whereas
the green regions signify the neutral electrostatic potential. The
MEP surface map of peppermint compounds provides necessary
information about reactive sites. These results can be used for
design and development of the stable peppermint-derived drugs.
The importance and application of MEP map in drug development
is discussed in many studies [114-117].
Nowadays, the development of phytotherapies aiming at
the inhibition of viral diseases , in combination with classical anti-viral therapies, is among the most intensively
studied approaches for the treatment of pathogenic viruses
. Infectious viral diseases remain an important worldwide
problem, since many viruses have resisted prophylaxis or therapy
longer than other microorganisms . At the moment, only
few effective antiviral drugs are available for the treatment of
viral diseases . There is need to find new compounds with
not only intracellular but also extracellular antiviral properties
. There are several reports showed that various peppermint
extracts has signiﬁcant antiviral activities [123-126]. It seems,
peppermint helps to immune system and protect the body from
viruses [127-137]. Table 5 presents a comprehensive list of
antivirus effect of peppermint extracts.
|Influenza A virus
|Newcastle disease virus
|VACV in egg
|West Nile viruses
||Influenza A virus
Table 5 Antiviral activity of different peppermint extracts.
Medicinal plants have been broadly used in common medicine
and therefore, plant secondary metabolites are increasingly
of interest as antimicrobial agents today [138,139]. Currently,
biologically active compounds from peppermint sources
have always been a great interest for scientists working on
infectious diseases . PO and extracts showed a good
antimicrobial activity against: 1) Escherichia coli, 2) Salmonella
pullorum, 3) Comamonas terrigena, 4) Streptococcus faecalis, 5) Acinatobacter sp, 6) Streptococcus thermophiles, 7) Lactobacillus
bulgaricus, 8) Staphylococcus pyogenes, 9) Staphylococcus
aureus, 10) Streptococcus pyogenes, 11) Serratia marcescens,
12) Mycobacterium avium, Salmonella typhi, 13) Salmonella
paratyphi A/B, 14) Proteus vulgaris, 15) Enterobacter aerogenes,
16) Yersinia enterocolitica and 17) Shigella dysenteriae
[131,141-143]. Studies showed that the antibacterial activity
of peppermint leaves extract against Gram negative bacilli
was higher than of its stem extract . A number of studies
demonstrated that essential oil from leaves of peppermint
exhibited the highest antibacterial activity with 11.58 to 17.24
mm ± 0.87 SD, zone of inhibition [1,62,125,133], while the effect
of extract obtained from the stem of peppermint is an average
zone of inhibition 15.82 mm ± 3.56 SD, respectively . On the
other hand, PO has strongly effects against Enterococcus faecium
ATCC10541, Salmonella choleraesuis, Staphylococcus aureus and Bacillus subtilis [140- 144]. There are differences in the chemical
composition of peppermint essential oil from different parts of
its structure . As mentioned above, this differences can
be effect on antibacterial activity of peppermint species .
Generally, mint oil and menthol have moderate antibacterial
effects against both Gram-positive/negative bacteria .
It seems peppermint can become a novel target for synthesis
of plant-derived drugs against a large spectrum of multidrug
In-vitro data suggested that PO and extracts are good fungicidal
against Candida albicans, Aspergillus albus and dermatophytic
fungi . The leave oils of Mentha spicata exhibited moderate
activity against Aspergillus fumigatus (with 16 mm ± 0.5 SD, zone
of inhibition) and A. niger (with 14 mm ± 0.5 SD) .
Allelopathy is one kind of stress that plays a signiﬁcant role in
agro-ecosystems, and affects the growth, quality and quantity
of the crops [147,148]. It was reported that water extract of
peppermint (at concentration 10% v/v) is able to inhibits the
growth of the tomato seedlings . Skrzypek and Coworkers
, demonstrated that aqueous extracts of peppermint (at
concentration 15% v/v) decreases non-photochemical and photochemical quenching and vitality index of photosystem
II in sunflower.
Currently, PO has become most considered agent as treatment for a large body of human diseases . The major health benefits
of PO are shown in (Figure 6). In addition to medicinal uses, its
extract is broadly used as flavoring in food industries . As
mentioned in pervious sections, among all chemical compounds that purified from PO , menthol is common ingredient and
widely is used for respiratory congestion [152,153], headache
, and skeletal muscle pain . The best dosage of PO for
consumption in adult was reported 0.2 to 0.4 mL of oil three
times daily in enteric-coated capsules .
Figure 6: The major health benefits of PO.
Angiogenesis, the formation of new arterioles from preexisting
vessels, is a multistep event involving degradation and
remodeling of the underlying basement membrane and the
surrounding extracellular matrix with subsequent proliferation
and migration of vascular endothelial cells into the tissue to
be vascularized [157-159]. Inflammation is regarded as an
important baseline reaction responsible for manifestations of
various chronic diseases such as cancer, septic shock, diabetes,
atherosclerosis and obesity [18,160]. Recent data have expanded
the concept that inflammation is a critical component of tumor
progression . There are several reports that peppermint
compounds have crucial roles in prevention of inflammation and
angiogenesis [161-163]. Methanol extract of peppermint has
cytotoxic effect on L1210 cancer cells . Lin and colleagues
 showed that apparently menthol, in higher doses, effects
on NAT activity in the human liver tumor cell line J5 .
The NAT is responsible for the biotransformation of numerous
arylamine drugs and carcinogens . This enzyme has three
critical residues consist of Cys68, His107 and Asp122 . These
residues corresponding to active site of NAT enzyme .
Herein, we performed a molecular docking to find the binding
mode of peppermint compounds into NAT enzyme as receptor
Figure 7: Representation of peppermint compounds docked with NAT enzyme as a receptor. (A) Cineole (B) Menthol (C) Menthyl acetate (D) Isopulegol (E) Menthone and (F) Carvone.
Docking results showed that cineole and menthyl acetate
interact with His107 residue and therefore, they are able to inhibit
NAT enzyme activity (Figure 7A and 7C). The docking energies
for cineole, menthol, menthyl acetate, isopulegol, menthone
and carvone were -11.2, -13.4, -11.91, -9.82, -7.83 and -10.11
kcal/mol, respectively. The His107 is one of critical residues in
the active site of NAT enzyme and it is important for its activity
. Lin and Co-workers  reported that menthol a possible
uncompetitive inhibitor to NAT activity in cytosols. Our docking
result showed that menthol is able to interact with two residues
(Tyr94 and Thr96) from NAT enzyme with a great probability
(Figure 7B). In other hand, menthon was also able to interact with these two residues from NAT enzyme (Figure 7E). Other
docked compounds (i.e. isopulegol and carvone) interact with
different residues of receptor (Figure 7D and 7F).
PO relaxes gastrointestinal smooth muscle  by reducing
calcium influx in both large intestine and jejunum . PO and
menthol are inhibitor for calcium channel activity in rats and guinea pig atrial and papillary muscle, rat brain synaptosomes,
and chick retinal neurons [171,172].
Treating Irritable Bowel Syndrome
IBS is defined as a chronic disorder of altered bowel function
characterized by symptoms of diarrhea, constipation, or
alternating bowel habits accompanied by pain or discomfort and
may include a constellation of other symptoms, e.g., bloating,
urgency, and incomplete evacuation [156,171,173-175]. This syndrome affects 9 to 23% of the population across the world
. It was reported that PO is a safe and effective short-term
treatment for IBS [177,178]. Also, PO acts as inhibitor for calcium
channel activity in the intestine and therefore it can able to reduce
symptoms of IBS . Other postulated mechanisms for PO in
treatment of IBS include inhibition of potassium depolarizationinduced
and electrically stimulated responses in the ileum .
Also, it was reported that PO has crucial effects on histamine,
serotonin, and cholinergic receptors in the gastrointestinal tract
may also mediate some of its antiemetic effects . Cappello
et al. showed that a four weeks treatment with PO improved
abdominal symptoms in patients with IBS . The similar
results also were reported in other studies [176,182-184]. Taken
together, peppermint is the most encouraged plant for treatment
of gastrointestinal disorders.
Since ancient times, herbal therapy has been used as treatment
for headache disorders . Consumption of peppermint and
derivatives is the best target for headache therapy . Gobel
et al. showed some beneﬁt from peppermint and eucalyptus oil
in combination in relieving patients’ headache pain . Also,
similar result was reported by Levin .
Effect on hepatic enzymes
Maliakal and Wanwimolruk reported that aqueous extract of
peppermint (at concentration 2% v/v) can modulate of phase I
and phase II drug metabolizing enzymes . In phase I, a variety
of enzymes act to introduce reactive and polar groups into their
substrates . Phase II biotransformation reactions generally
serve as a detoxifying step in drug metabolism . Khodadust
et al. showed that peppermint alcoholic extract ameliorated the
adverse effects of CCl4 on growth performance and liver function,
therefore they indicated that it might be useful for the prevention
of oxidative stress-induced hepatotoxicity in broilers .
The radioprotective activity of peppermint oil and aqueous
extract has well been documented [192,193]. Kaushik et al.
demonstrated the effectiveness of peppermint alcoholic extract
against radiation induced morbidity and mortality using the
optimum dose of 100 mg/kg for 3 consecutive days .
Samarth and Coworkers suggested the antioxidant and free radical scavenging activities of leaf extract of peppermint are
directly related to its mechanism of radiation protection .
Several mechanisms such as antioxidant activity, immune response,
and enhanced recovery of bone marrow have been suggested for
chemoprevention and radioprotection of peppermint extracts .
Side Effects and Toxicity
Although peppermint is a considered medicinal plant for
treatment of human diseases, it was reported that in rats, PO
caused cyst-like changes in the white matter of the cerebellum
and nephropathy at doses of 40-100 mg/kg per day for 28-90
Adverse reactions to enteric coated PO capsules are rare ,
but may include hypersensitivity reaction, contact dermatitis,
abdominal pain, heartburn, perianal burning, bradycardia and
muscle tremor [175,196].
In patients with chronic cough, pre-inhalation of menthol reduces
cough sensitivity to inhaled capsaicin and inﬂuences inspiratory
ﬂows . In rats, doses of 80 and 160 mg of pulgeone for 28
days caused atonia, weight loss, decreased blood creatinine
content, and histopathological changes in the liver and the white
matter of the cerebellum . Menthol causes hepatocellular
changes in rats .
The market for PO in the entire world is divided into local and
international buyers. The local buyers included small buyers
and companies from chemical and pharmaceutical, as well
as food and flavoring industries. The international buyers are
divided into flavor and fragrance houses, cosmetics and personal
health care, aromatherapy and food manufacturers who buy in
large quantities . The peppermint industry is the largest
commercial herb industry in the United States (more than 4000
tons per year). Keeping in view multiple benefits of peppermint,
various dosage forms are available in market for treatment of
various human lifestyle diseases (Figure 8).
Figure 8: Different dosage forms of PO alone or in combination with other chemical ingredients are available in market.
Regarding to health benefits of peppermint, it can be concluded
that this plant has great potentials for treatment of human
diseases and also it has strong future in the world marketing.
Further studies are need to exploration of cellular and molecular
mechanisms of peppermint and its compounds on human body.
Although peppermint plant has great beneficial and economical
role in human society, researches must be considered its minor
side effects and toxicity. The future in vivo human studies are
needed to determine the molecular mechanism of PO in human
health. Currently PO is most frequently traded essential oil in the
entire world and in many developed and developing countries it
considered as a valuable target for both food and pharmaceutical
We gratefully thank Yoshihiro Kawaoka (editor in chief of Journal
of Archives of Clinical Microbiology) for his kind invitation to
write the current manuscript.
Conflicts of Interest
Authors certify that no actual or potential conflict of interest in
relation to this article exists.
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